This review of published studies was conducted to derive data on patients with congenital
fibrinogen deficiency (CFD), including dosing of
fibrinogen replacement
therapy, outcome, and adverse events, either temporally related or distant to
fibrinogen replacement, in order to assist clinicians in developing treatment plans for patients with CFD. A systematic review was performed of case reports identified by a MEDLINE search between 1961 and 2010. Eligible studies included subjects with a diagnosis of CFD who received
fibrinogen replacement. An attempt was made to extract dose, frequency, duration,
hemostatic efficacy and adverse events such as
thrombosis or
allergic reactions. Reported thrombotic events distant from
fibrinogen replacement were also recorded. From 104 papers reviewed, a total of 50 cases were identified:
afibrinogenemia (35), hypofibrinogenemia (6), and dysfibrinogenemia (9).
Fibrinogen replacement
therapy was generally effective in preventing or treating
bleeding in doses adequate to achieve and maintain
fibrinogen activity above 50-100 mg dL(-1) (non-surgical and obstetric use) or 100-200 mg dL(-1) (surgical prophylaxis). Increased
fibrinogen clearance was observed with massive
hemorrhage, major surgery, and advanced pregnancy. Obstetric outcomes were optimized when
fibrinogen replacement was initiated prior to conception. Uncontrolled
hemorrhage,
allergic reactions and antibody formation were rare events. However,
thromboses, both related and unrelated to
fibrinogen replacement, occurred in 15 of 50 (30%) patients overall, and in eight of 12 (67%) adult non-obstetric patients with
afibrinogenemia. Published
fibrinogen replacement regimens are presented for 50 CFD patients.
Fibrinogen replacement
therapy requires careful monitoring of
fibrinogen levels.
Afibrinogenemia is associated with thromboembolic complications with or without treatment.